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Remdesivir has been reported to speed time to recovery in people with severe COVID-19, but more-effective treatments are needed. Investigators have now conducted a phase 2, randomized, open-label trial comparing triple therapy (with the combination of interferon-beta, lopinavir/ritonavir and ribavirin) to lopinavir/ritonavir alone (control therapy) in people hospitalized with COVID-19 in Hong Kong.
Among 127 participants, 86 were randomized to combination therapy and 41 to control therapy. In the combination-therapy group, those admitted <7 days after symptom onset (n=52) received interferon-beta, ribavirin, and lopinavir/ritonavir, whereas interferon-beta was omitted from combination therapy in those admitted ≥7 days after symptom onset (n=34) because of theoretic concerns regarding its proinflammatory effects during this phase of COVID-19.
The combination-therapy group had a shorter time to negative nasopharyngeal swab test than the control group (7 days vs. 12 days). Clinical improvement, according to two scales (NEWS2 and SOFA), occurred more rapidly in the combination group than in the control group. The combination group had shorter mean hospitalization duration than the control group (9.0 days vs. 14.5 days); discharge required negative polymerase chain reaction (PCR) tests.
Hung IFN et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: An open-label, randomised, phase 2 trial. Lancet 2020 May 8; [e-pub]. (https://doi.org/10.1016/S0140-6736(20)31042-4)
Comment
There are several caveats regarding the positive results of this study. First, the participants were not particularly ill; only about 12% to 14% received oxygen supplementation and only one person was placed on a ventilator. Second, detailed information on the clinical improvement with combination therapy is not given, and the open-label design may have influenced assessments. Finally, the beneficial clinical impact of the combination treatment was limited to those hospitalized <7 days after symptom onset. Moreover, the duration of PCR positivity in both groups in this trial was shorter than reported in other studies (Lancet 2020; 395:1054 and NEJM JW Infect Dis Jun 2020 and Nature 2020 Apr 1; [e-pub]); indeed, many of us are seeing people with prolonged RNA shedding in our practice. People with less-severe disease — like those in this trial — may have shorter duration of PCR positivity, independent of the treatment received, but more information is needed. How this combination performs in people with more-severe COVID-19, and how it compares to remdesivir, would be interesting to see.